| Author | Matteucci, Kely Catarine | |
| Author | Assis, Patricia A. | |
| Author | Hirako, Isabella Cristina | |
| Author | Leite, Nathalia P. S. | |
| Author | Pioto, Franciele | |
| Author | Ojelabi, Ogooluwa | |
| Author | Toller-Kawahisa, Juliana E. | |
| Author | Costa, Diego Luis | |
| Author | Silva, João S. | |
| Author | Alves-Filho, Jose C. | |
| Author | Gazzinelli, Ricardo Tostes | |
| Access date | 2024-06-27T14:53:52Z | |
| Available date | 2024-06-27T14:53:52Z | |
| Document date | 2024 | |
| Citation | MATTEUCCI, Kely Catarine et al. Reprogramming of host energy metabolism mediated by the TNF-iNOS-HIF-1alpha axis plays a key role in host resistance to Plasmodium infection. bioRxiv, p. 1-37, 2024. | |
| URI | https://www.arca.fiocruz.br/handle/icict/64707 | |
| Language | eng | en_US |
| Rights | restricted access | |
| Subject in Portuguese | Glucose | pt_BR |
| Subject in Portuguese | TNF | pt_BR |
| Subject in Portuguese | iNOS | pt_BR |
| Subject in Portuguese | HIF-1α | pt_BR |
| Title | Reprogramming of host energy metabolism mediated by the TNF-iNOS-HIF-1alpha axis plays a key role in host resistance to Plasmodium infection | en_US |
| Type | Preprint | |
| DOI | 10.1101/2024.03.26.586751 | |
| Abstract | TNF has a dual effect in Plasmodium infection, bolstering the host’s immune defense while also triggering disease. Here, we show that TNF signaling hampers physical activity, food intake, and energy expenditure while enhancing glucose uptake by the liver and spleen as well as controlling parasitemia in P. chabaudi (Pc)-infected mice. We also demonstrate that TNF is required for expression of inducible nitric oxide synthase (iNOS), stabilization of HIF-1α, expression of glucose transporter GLUT1 and enhanced glycolysis in monocytic cells from Pc-infected mice. Importantly, Pc- infected iNOS-/-, TNFRΔLyz2 and HIF-1αΔLyz2 mice show impaired release of TNF and glycolysis in monocytes, together with increased parasitemia and disease tolerance. Together, our findings reveal that TNF-iNOS-HIF-1α-induced glycolysis in monocytes plays a critical role in host defense and sickness behavior in Pc-infected mice. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Presidência. Vice-presidência de Pesquisa e Coleções Biológicas. Plataforma de Medicina Translacional. Rio de Janeiro, RJ, Brazil / Department of Biochemistry and Immunology. Ribeirão Preto Medical School. University of São Paulo. São Paulo, SP, Brazil. | |
| Affilliation | Department of Pathology. University of Michigan Medical School. Ann Arbor, USA. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil. | |
| Affilliation | Fundação Oswaldo Cruz. Presidência. Vice-presidência de Pesquisa e Coleções Biológicas. Plataforma de Medicina Translacional. Rio de Janeiro, RJ, Brazil /Department of Biochemistry and Immunology. Ribeirão Preto Medical School. University of Sao Paulo. Ribeirão Preto, SP, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Presidência. Vice-presidência de Pesquisa e Coleções Biológicas. Plataforma de Medicina Translacional. Rio de Janeiro, RJ, Brazil | |
| Affilliation | Department of Medicine. Division of Infectious Diseases and Immunology. University of Massachusetts Chan Medical School. Worcester, MA, USA. | |
| Affilliation | Departament of Pharmacology. Ribeirão Preto Medical School. University of Sao Paulo. Ribeirão Preto, SP, Brazil. | |
| Affilliation | Department of Biochemistry and Immunology. Ribeirão Preto Medical School. University of Sao Paulo. Ribeirão Preto, SP, Brasil / Department of Immunology. Institute of Biomedical Sciences. University of Sao Paulo. Ribeirão Preto, SP, Brasil | |
| Affilliation | Fundação Oswaldo Cruz. Presidência. Vice-presidência de Pesquisa e Coleções Biológicas. Plataforma de Medicina Translacional. Rio de Janeiro, RJ, Brazil. | |
| Affilliation | Departament of Pharmacology. Ribeirão Preto Medical School. University of Sao Paulo. Ribeirão Preto, SP, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Presidência. Vice-Presidência de Pesquisa e Coleções Biológicas. Plataforma de Medicina Translacional. Rio de Janeiro, RJ, Brazil / University of São Paulo. Ribeirão Preto, SP, Brasil / Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil / Department of Medicine. Division of Infectious Diseases and Immunology. University of Massachusetts Chan Medical School. Worcester, MA, USA. | |
| Subject | Glucose | en_US |
| Subject | TNF | en_US |
| Subject | iNOS | en_US |
| Subject | HIF-1α | en_US |
| Subject | Monocytic cells | en_US |
| Subject | P. chabaudi | en_US |
| Subject | Myeloid cells | en_US |
| Subject | Malária | en_US |
| Embargo date | 2030-12-31 | |
